Currently, the treatment of diabetes, both type 1 diabetes and type 2 diabetes, relies to an increasing extent on the so-called intensive insulin treatment. According to this regimen, the patients are treated with multiple daily insulin injections comprising one or two daily injections of a long acting insulin to cover the basal insulin requirement supplemented by bolus injections of a rapid acting insulin to cover the insulin requirement related to meals.
Long acting insulin compositions are well known in the art. Thus, one main type of long acting insulin compositions comprises injectable aqueous suspensions of insulin crystals or amorphous insulin. In these compositions, the insulin compounds utilized typically are protamine insulin, zinc insulin or protamine zinc insulin.
Certain drawbacks are associated with the use of insulin suspensions. Thus, in order to secure an accurate dosing, the insulin particles must be suspended homogeneously by gentle shaking before a defined volume of the suspension is withdrawn from a vial or expelled from a cartridge. Also, for the storage of insulin suspensions, the temperature must be kept within more narrow limits than for insulin solutions in order to avoid lump formation or coagulation.
International patent application WO 2006/082204 (Novo Nordisk A/S) discloses insulin derivatives having an aromatic group in the side chain.
Patent application WO 2006/082205 (Novo Nordisk A/S), disclose insulin derivatives having a PEG in the side chain.
Insulin derivatives with a charged terminal group in the substituent are disclosed in international patent application no. EP2007/054444 (Novo Nordisk A/S).
However, there is still a need for insulin having a more prolonged profile of action than the insulin derivatives known up till now.